Learning Rules for Spike Timing-Dependent Plasticity Depend on Dendritic Synapse Location

Abstract

Previous studies focusing on the temporal rules governing changes in synaptic strength during spike timing-dependent synaptic plasticity (STDP) have paid little attention to the fact that synaptic inputs are distributed across complex dendritic trees. During STDP, propagation of action potentials (APs) back to the site of synaptic input is thought to trigger plasticity. However, in pyramidal neurons, backpropagation of single APs is decremental, whereas high-frequency bursts lead to generation of distal dendritic calcium spikes. This raises the question whether STDP learning rules depend on synapse location and firing mode. Here, we investigate this issue at synapses between layer 2/3 and layer 5 pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of single APs at positive times leads to a distance-dependent shift to long-term depression (LTD) at distal inputs. At proximal sites, this LTD could be converted to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a progressive, distance-dependent shift in the timing requirements for induction of LTP and LTD, such that distal synapses display novel timing rules: they potentiate when inputs are activated after burst onset (negative timing) but depress when activated before burst onset (positive timing). These findings could be explained by distance-dependent differences in the underlying dendritic voltage waveforms driving NMDA receptor activation during STDP induction. Our results suggest that synapse location within the dendritic tree is a crucial determinant of STDP, and that synapses undergo plasticity according to local rather than global learning rules.

Dendritic Compartment and Neuronal Output Mode Determine Pathway-Specific Long-Term Potentiation in the Piriform Cortex

“…Factors determining spine Ca 2ϩ reduction in layer 1a are (1) the failure of the bAP to relieve the Mg 2ϩ block of the NMDAR, and (2) a smaller VGCC-mediated Ca 2ϩ influx. In distal dendrites of neocortical and hippocampal CA1 pyramidal cells, the induction of LTP by pairing EPSPs with subsequent APs is impaired (Golding et al, 2002;Letzkus et al, 2006;Sjöström and Häusser, 2006). Consistent with this, we were only able to induce LTP by pairing EPSPs with subsequent AP bursts in the proximal layer 1b.…”

“…In pyramidal cells in CA1 and the neocortex, the supralinear spine Ca 2ϩ responses are considered to be the elementary building blocks of LTP induction, with paradigms based on pairing EPSPs with subsequent bursts of APs (Pike et al, 1999;Letzkus et al, 2006;Nevian and Sakmann, 2006). We wanted to relate the observed differences between spine Ca 2ϩ responses in layer 1a and those in layer 1b to the induction of LTP.…”

“…The induction of LTP by pairing EPSPs with subsequent action potentials (APs) is reduced in the distal dendrites in neocortical pyramidal cells and in the CA1 pyramidal cells in the hippocampus. In these neurons, the attenuated distal propagation of backpropagating APs (bAPs), mediated by the intrinsic electrical properties of the dendritic tree, weakens distal LTP induction (Golding et al, 2002;Letzkus et al, 2006;Sjöström and Häusser, 2006).…”

“…In area CA1 within the hippocampal formation and also the neocortex, LTP can be induced by pairing EPSPs with bursts of APs (Pike et al, 1999;Letzkus et al, 2006;Nevian and Sakmann, 2006). It has been demonstrated by Suzuki and Bekkers that intrinsic AP bursting during suprathreshold depolarization is a key feature of piriform cortex pyramidal cells.…”

Burst-Induced Anti-Hebbian Depression Acts through Short-Term Synaptic Dynamics to Cancel Redundant Sensory Signals

“…Such analyses might also shed light on the more general relation between diverse underlying cellular mechanisms and the functional effects of different LTD rules on information transfer in neural networks (Egger et al, 1999;Phares et al, 2003;Birtoli and Ulrich, 2004;Tzounopoulos et al, 2004Tzounopoulos et al, , 2007Letzkus et al, 2006;Caporale and Dan, 2008).…”